One of the most profilic stereoselective reactions is the nucleophilic attack on carbonyl compounds. These compounds have two stereogenic faces and, thus, it is a question on which face will the attack preferentially take place. In this respect two empirical rules have been developed which predict the same result.

 

• Cram’s rule: According to this rule, if the molecule is observed along the axis, (represented as shown below), where S, M and L stand for small, medium and large, respectively. The oxygen of the carbonyl orients itself between the small and the medium sized groups. The rule is that the incoming group preferentially attacks on the side of the plane containing the small group (Scheme 8).

Scheme 8

But, when chelation may occur between the carbonyl oxygen and the counteraction of the incoming nucleophile, then the result of Cram’s rule may be reversed. In this case the large group chelates counter cation of attacking nucleophile and carbonyl oxygen.

• Felkin Ahn model: The statement of the rule is same as that of Cram’s rule but the objective is achieved by reasoning from a different angle. Assuming that there isn’t an unusually electronegative atom on the carbon next to the carbonyl, the largest group (L) prefers a conformation where it is perpendicular to the carbonyl C=O. This gives two relatively competitive lowest energy conformations, with the medium (M) and smallest (S) groups differing in their proximity to the carbonyl oxygen.

It is further determined that the nucleophile prefers to attack away from the large group at an angle of 107°. Thus, it attacks nearer to the small (S) group giving rise to only one diastereomer.